| 1. |
- Eriksson, Erik, 1977-, et al.
(författare)
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The pitfalls of a popular concept : Co-production in times of individualization, marketization, and de-politicization
- 2023
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Ingår i: Scandinavian Journal of Public Administration. - 2001-7405 .- 2001-7413. ; 27:3, s. 87-107
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Tidskriftsartikel (refereegranskat)abstract
- Co-production between public administrators and citizens has attracted renewed interest in recent years. Co-production is predominantly perceived as something desirable and is claimed to improve service efficiency and outcome and user satisfaction, at the same time as addressing democratic ideals. Drawing from interviews with public administrators and patients in a Swedish healthcare context, this paper seeks to nuance the often overly positive notion of co-production by understanding these micro-level practices as being embedded in a macro-level societal context. Theorizing the empirical material based on three features of contemporary society –individualization, marketization, and de-politicization –we argue that co-production risks placing a burden and responsibility on individual users and creating a (welfare)market in which better-off people are recruited and benefitted. In this sense, co-production may consolidate or reinforce inequalities. Through de-politicization, political issues may appear as value-free; however, as long as market-logics prevail, the welfare system and practices of co-production will, in some respects, be impotent to address crucial societal issues. Co-production as a collective practice targeting democratic standards is called for, rather than an efficiency focus, preferably by taking the recruitment of those in the greatest need seriously –scaffolded by a revitalized public service ethos of public administrators and their organizations.
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| 2. |
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| 3. |
- Holmgren, Jan, 1944, et al.
(författare)
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Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA
- 2005
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Ingår i: Immunology Letters. - : Elsevier. - 0165-2478 .- 1879-0542. ; 97:2, s. 181-8
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal immunisation may be used both to protect the mucosal surfaces against infections and as a means for immunological treatment of peripheral immunopathological disorders through the induction of systemic antigen-specific tolerance ('oral tolerance'). The development of mucosal vaccines, whether for prevention of infectious diseases or for oral tolerance immunotherapy, requires efficient antigen delivery and adjuvant systems that can help to present the appropriate vaccine or immunotherapy antigens to the mucosal immune system. The most potent (but also toxic) mucosal adjuvants are cholera toxin (CT) and the closely related Escherichia coli heat-labile enterotoxin (LT), and much effort and significant progress have been made recently to generate toxicologically acceptable derivatives of these toxins with retained adjuvant activity. Among these are the non-toxic, recombinantly produced cholera toxin B-subunit (CTB). CTB is a specific protective antigen component of a widely registered oral cholera vaccine as well as a promising vector for either giving rise to mucosal anti-infective immunity or for inducing peripheral anti-inflammatory tolerance to chemically or genetically linked foreign antigens administered mucosally. CT and CTB have also recently been used as combined vectors and adjuvants for markedly promoting ex vivo dendritic cell (DC) vaccination with different antigens and also steering the immune response to the in vivo-reinfused DCs towards either broad Th1 + Th2 + CTL immunity (CT) or Th2 or tolerance (CTB). Another type of mucosal adjuvants is represented by bacterial DNA or synthetic oligodeoxynucleotides containing CpG-motifs, which especially when linked to CTB have been found to effectively stimulate both innate and adaptive mucosal immune responses. The properties and clinical potential of these different classes of adjuvants are being discussed. © 2004 Elsevier B.V. All rights reserved.
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| 4. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 5. |
- Olsson, Erik, 1977, et al.
(författare)
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When one size does not fit all: Using participatory action research to co-create preventive healthcare services
- 2015
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Ingår i: Action Research. - : SAGE Publications. - 1741-2617 .- 1476-7503. ; 13:1, s. 9-29
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Tidskriftsartikel (refereegranskat)abstract
- Organized screening programs have proved effective at reducing cervical cancer inSweden by offering early detection of precancerous cells. However, participationrates vary across groups of women. The purpose of this paper is to explore howparticipatory action research contributes to (re)designing cervical cancer screeningprograms to better meet local residents’ needs and expectations. The paper examinesthe Pap smear testing barriers encountered by foreign-born women. It is also reportedhow different actors within the healthcare system as well as civil society can worktogether to address these barriers and improve healthcare services. Moreover, thepaper contributes to action research methodology by demonstrating how participatoryinquiries benefit from quantitative monitoring of improvement initiatives.
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| 6. |
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| 7. |
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| 8. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 9. |
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| 10. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 12. |
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| 13. |
- Ekström, Erik, 1989-
(författare)
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Growth and thermoelectric properties of CaMnO3-based thin films
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of them1oelectrics started in early 19th century. Since the discovery of the Seebeck effect and the Peltier effect, thermoelectric modules have found their way into, mostly, niche applications such as radioisotope thermoelectric generators on space missions. Thermoelectric modules can also be used for cooling, utilizing the Peltier effect.Thermoelectrics are promising materials due to the operation nature of the modules. That is, they have no moving parts, no exhaust, long lifetime without maintenance, features that make them attractive for many applications. Despite these promising properties, thermoelectric modules are mostly used in niche applications. The main reason for this is conventional modules with the highest efficiency are commonly made of expensive and/or rare elements which prevents mass production.To tackle this problem, new materials are investigated to find a module that can be made widely available. Oxides are one possibility, where an added benefit is that they are chemically stable even at elevated temperature. The perovskite CaMnO3 is one of the more promising oxides, with elements that are abundant on earth and cheap. The material does suffer from low electrical conductivity which results in a low electrical conductivity and efficiency. A substantial effort has been put in to increase the efficiency of CaMnO3, hut it still needs improvement.In my thesis, I have investigated the CaMnO3 system. CaMnO3 was synthesized using co-reactive RF-magnetron sputtering and post annealing. The synthesis method is already known hut has not been used for deposition of perovskites. I have also demonstrated that this synthesis method can be used to dope CaMnO3 with niobium at appropriate levels for enhancing the efficiency.
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| 14. |
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| 15. |
- Eriksson, Daniel, 1984-, et al.
(författare)
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Flywheel angular velocity model for misfire and driveline disturbance simulation
- 2013
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Ingår i: Proceedings of the 7th IFAC Symposium on Advances in Automotive Control, The International Federation of Automatic Control. - : Elsevier. ; , s. 570-575
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Konferensbidrag (refereegranskat)abstract
- A flywheel angular velocity model for misfire and disturbance simulation is presented. Applications of the model are, for example, initial parameter calibration and robustness analysis of misfire detection algorithms. An analytical cylinder pressure model is used to model cylinder torque and a multi-body model with torsional flexibilities is used to model crankshaft and driveline oscillations. Misfires, cylinder variations, changes in auxiliary load, and flywheel manufacturing errors can be injected in the model and the resulting speed variations can be simulated. A qualitative validation of the model shows that simulated angular velocity captures the amplitude and oscillatory behavior of measurement data and the effects of different phenomena, such as misfire and flywheel manufacturing errors.
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| 16. |
- Eriksson, Erik, 1977-, et al.
(författare)
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Public management in turbulent times : COVID-19 as an ecosystem disruptor
- 2021
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Ingår i: Australian journal of public administration. - : John Wiley and Sons Inc. - 0313-6647 .- 1467-8500. ; 80:4, s. 732-747
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Tidskriftsartikel (refereegranskat)abstract
- The decentralisation of Swedish healthcare closer to citizens has been slow. Drawing from empirical material of the reform prior and amidst the COVID-19 pandemic, this paper argues that the pandemic has disrupted the healthcare ecosystem. Consequently, citizen-centred collaborations have accelerated integration of resources (such as knowledge and skills) across organisational, hierarchical and professional borders. However, collaborations have been delimited to traditional healthcare providers, neglecting the resources of citizens and other actors to be used to improve service delivery. The pandemic has revealed strengths and weaknesses with the prevailing healthcare ecosystem that post-COVID-19 public management must address, both theoretically and practically. Theoretically, the paper contributes to the development of a public service logic, addressing both strengths and difficulties with the logic in turbulent times. Practically, the empirical descriptions contribute to improved understanding of public service delivery reform and how it is impacted during the pandemic. © 2021 The Authors. Australian Journal of Public Administration published by John Wiley & Sons Australia, Ltd on behalf of Institute of Public Administration Australia.
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| 17. |
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| 18. |
- Gyllenhammar, Daniel, 1994, et al.
(författare)
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Theory and practice of customer-related improvements: a systematic literature review
- 2023
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Ingår i: Total Quality Management and Business Excellence. - : Informa UK Limited. - 1478-3371 .- 1478-3363. ; 34:1-2, s. 201-219
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Tidskriftsartikel (refereegranskat)abstract
- Customers are vital to any organization and system, and must therefore be considered when seeking to improve. However, how to improve with regard to the customer, is not clear, and the knowledge is spread over several research fields, making it difficult for researchers and practitioners to comprehend. The purpose of this literature review is to show how customer-related improvements are described in the literature and how the research is performed. 666 articles were screened, resulting in 99 coded and analysed articles. The study concludes that there is a lack of understanding when it comes to the process of how to improve and that both practitioners and academics should focus more on the system level. It is also seen that by involving the customer in the improvement process, the improvement is more likely to succeed. The article concludes that there is a need for future research which are conceptual, longitudinal, and are addressing actual improvements, not just potential. From the practitioners' point of view, the article is proposing an increased focus on customer-related improvements which address aspects concerning people, such as employee competence and work environment, and reward systems, rather than strategy and processes to improve the potential benefits.
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| 19. |
- Gyllenhammar, Daniel, 1994, et al.
(författare)
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Value creation and destruction involving multiple public service organizations: a focus on frontline employees
- 2023
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Ingår i: Public Management Review. - 1471-9037 .- 1471-9045.
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Tidskriftsartikel (refereegranskat)abstract
- Using six focus groups with frontline employees within the Swedish sick-leave service, this article explores the co-creation/destruction of value. The article both adheres to and questions the public service logic by utilizing an empirical case in which frontline staff represents not one, but multiple, public service organizations. Moreover, as value creation/destruction is not restricted to one beneficiary, and several beneficiaries can be tied to one single service, the research builds upon this notion and distinguishes between four levels of value creation/destruction.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Lind, Lars, et al.
(författare)
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Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
- 2022
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Smith, Frida, 1973, et al.
(författare)
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Exploring the meaning, role and experiences of a patient-led social innovation for people affected by cancer: a new collaborative care model complementing traditional cancer rehabilitation in Sweden
- 2021
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Ingår i: BMJ open quality. - : BMJ. - 2399-6641. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective Kraftens Hus is the first support centre in Sweden designed by and for people affected by cancer, including patients, family, friends, staff members and local community representatives (collectively 'stakeholders'). The purpose of this study was to explore the meaning, role and experiences of Kraftens Hus stakeholders using a patient and public involved methodology. Methods To understand and map the experiences of visitors to Kraftens Hus, we applied concept mapping (CM), a mixed methods approach where data are collected and analysed in four structured steps designed to capture the diverse perspectives of multiple stakeholders. Qualitative interviews with relevant stakeholders supplemented the CM findings. Results The final concept map contained six clusters of ideas. Within the clusters, there was a recurring theme that cancer-affected people value accessible and long-term psychosocial support (PSS). The intended emotional, social and practical needs identified in a previous design process seem to have been addressed and appreciated by Kraftens Hus visitors. Conclusion Kraftens Hus is an example of a new patient-led social innovation based on a life-event perspective and integration of resources from different sectors in society. By focusing on life, not the disease, the care continuum expands, and long-term PSS is provided alongside cancer treatment. The evaluation confirms that PSS should focus on health and well-being in the broadest sense.
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| 31. |
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| 32. |
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| 33. |
-
- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
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Tidskriftsartikel (refereegranskat)
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| 34. |
-
- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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| 35. |
- Andersson, Niklas, 1976, et al.
(författare)
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Numerical Simulation of Stirling Engines Using an Unsteady Quasi-One-Dimensional Approach
- 2015
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Ingår i: Journal of Fluids Engineering, Transactions of the ASME. - : ASME International. - 1528-901X .- 0098-2202. ; 137:5, s. Art. no. 051104-
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Tidskriftsartikel (refereegranskat)abstract
- An existing computer code for solving the quasi-one-dimensional flow equations governing unsteady compressible flow in tubes with smoothly varying cross-section areas, has been adapted to the simulation of the oscillatory flow in Stirling engines for engine design purposes. By utilizing an efficient smoothing algorithm for the area function that preserves the total volume of the tube, it has been possible to achieve a highly accurate and fully conservative numerical scheme. Sub-models for wall friction and heat transfer have been added, enabling the simulation of gas heaters, gas coolers, and regenerators. The code has been used for the modeling of an alpha-type Stirling engine and validated for a range of operating conditions with good results.
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| 36. |
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| 37. |
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| 38. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
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Serotonin transporter gene polymorphisms: Effect on serotonin transporter availability in the brain of suicide attempters
- 2008
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Ingår i: Psychiatry Research: Neuroimaging. - : Elsevier BV. - 0925-4927 .- 0165-1781. ; 162:3, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using I-123-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.
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| 39. |
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| 40. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Markers of systemic inflammation in preclinical ulcerative colitis
- 2019
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Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 7:8_suppl, s. 111-111
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.
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| 41. |
- Bergquist, Bjarne, et al.
(författare)
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Alive and kicking–but will Quality Management be around tomorrow? A Swedish academia perspective
- 2012
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Ingår i: Quality Innovation Prosperity. - : Technical University of Kosice, Faculty of Materials, Metallurgy and Recycling. - 1335-1745 .- 1338-984X. ; 16:2, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to describe how Quality Management (QM) is perceived today by scholars at three Swedish universities, and into what QM is expected to develop into in twenty years. Data were collected through structured workshops using affinity diagrams with scholars teaching and performing research in the QM field. The results show that QM currently is perceived as consisting of a set of core of principles, methods and tools. The future outlook includes three possible development directions for QM are seen: [1] searching for a “discipline X” where QM can contribute while keeping its toolbox, [2] focus on a core based on the traditional quality technology toolbox with methods and tools, and [3] a risk that QM, as it is today, may seize to exist and be diffused into other disciplines.
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| 42. |
- Bergstrand, Martin, 1977-, et al.
(författare)
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A semi-mechanistic model for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Methods to study in vivo gastro intestinal (GI) transit and/or regional absorption of pharmaceuticals are available and increasingly used in drug development. A modelling approach to utilize the information generated in such studies for prospective predictions of absorption from newly developed modified release formulations was outlined and tested for the investigational drug AZD0837. This work was a natural extension to the companion article “A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations”. The drug release model governed the amount of substance released in distinct GI regions over time. GI distribution of released drug substance, region specific rate and extent of absorption and the influence of concomitant food intake were estimated with the model. The model was informed by data from a magnetic marker monitoring study and an intubation study with local administration in colon. Disposition estimates were further supported by observations following administration of oral solution and intravenous infusion of AZD0837. Distinctly different absorption properties were characterized for different GI regions. Bioavailability over the gut-wall was estimated to be high for substance released in the stomach and absorbed in duodenum (70%) compared to substance released and absorbed in the small intestine (25%). Bioavailability was once again higher in colon (70%) but on the other hand considerably slower than in the earlier parts of the GI tract. The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.
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| 43. |
- Bergstrand, Martin, 1977-, et al.
(författare)
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A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In vivo prediction of drug release based on in vitro experiments is important for the development of new modified release (MR) formulations. Most efforts to improve such predictions have focused on altering the in vitro experiments to more resemble the in vivo conditions. A novel approach is evaluated in the present article where a computer model is established and used to link results from standard static in vitro experiment to in vivo predictions. A nonlinear mixed-effects model describing the in vitro drug release for 6 closely related hydrophilic matrix based MR formulations across different experimental conditions (pH, rotation speed and ionic strength) was developed. This model was applied to in vivo observations of drug release and tablet gastro intestinal (GI) position assessed with Magnetic Marker Monitoring (MMM). By combining the MMM observations with literature information on pH and ionic strength along the GI tract, the mechanical stress in different parts of the GI tract could be estimated in units equivalent to rotation speed in the in vitro set-up (USP 2 apparatus). The mechanical stress in the upper stomach was estimated to be 94 rpm and 134 rpm in the lower stomach. For the small intestine and colon the estimates of mechanical stress was 93 and 38 rpm respectively. Predictions of in vivo drug release including expected between subject/tablet variability could be made for other newly developed formulations based on the drug release model combined with a model describing tablet GI transit. This exemplifies a modeling approach that can be utilized to predict in vivo behavior from standard in vitro experiments and support formulation development and quality control of MR formulations.
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| 44. |
- Bergstrand, Martin, 1977-, et al.
(författare)
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A semi-mechanistic modeling strategy for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations
- 2012
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Ingår i: Pharmaceutical research. - : Springer Science+Business Media B.V.. - 0724-8741 .- 1573-904X. ; 29:2, s. 574-584
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To outline and test a new modeling approach for prospective predictions of absorption from newly developed modified release formulations based on in vivo studies of gastro intestinal (GI) transit, drug release and regional absorption for the investigational drug AZD0837. METHODS This work was a natural extension to the companion article "A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations". The drug release model governed the amount of substance released in distinct GI regions over time. GI distribution of released drug substance, region specific rate and extent of absorption and the influence of food intake were estimated. The model was informed by magnetic marker monitoring data and data from an intubation study with local administration in colon. RESULTS Distinctly different absorption properties were characterized for different GI regions. Bioavailability over the gut-wall was estimated to be high in duodenum (70%) compared to the small intestine (25%). Colon was primarily characterized by a very slow rate of absorption. CONCLUSIONS The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.
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| 45. |
- Bergstrand, Martin, 1977-, et al.
(författare)
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A Semi-mechanistic Modeling Strategy to Link In Vitro and In Vivo Drug Release for Modified Release Formulations
- 2012
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 29:3, s. 695-706
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop a semi-mechanistic model linking in vitro to in vivo drug release. METHODS: A nonlinear mixed-effects model describing the in vitro drug release for 6 hydrophilic matrix based modified release formulations across different experimental conditions (pH, rotation speed and ionic strength) was developed. It was applied to in vivo observations of drug release and tablet gastro intestinal (GI) position assessed with magnetic marker monitoring (MMM). By combining the MMM observations with literature information on pH and ionic strength along the GI tract, the mechanical stress in different parts of the GI tract could be estimated in units equivalent to rotation speed in the in vitro USP 2 apparatus. RESULTS: The mechanical stress in the upper and lower stomach was estimated to 94 and 134 rpm, respectively. For the small intestine and colon the estimates of mechanical stress was 93 and 38 rpm. Predictions of in vivo drug release including between subject/tablet variability was made for other newly developed formulations based on the drug release model and a model describing tablet GI transit. CONCLUSION: The paper outlines a modeling approach for predicting in vivo behavior from standard in vitro experiments and support formulation development and quality control.
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| 46. |
- Bergström, Göran, 1964, et al.
(författare)
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Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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| 47. |
- Blomberg, Jeanette, 1977-
(författare)
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Regulation of apoptosis during treatment and resistance development in tumour cells
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Induction of apoptosis is the most studied cell death process and it is a tightly regulated physiological event that enables elimination of damaged and unwanted cells. Apoptosis can be induced via activation of either the intrinsic or the extrinsic signalling pathway. The intrinsic pathway involves activation of the mitochondria by stress stimuli, whereas the extrinsic pathway is triggered by ligand induced activation of death receptors such as Fas. Apoptosis induction via Fas activation plays an important role in the function of cytotoxic T lymphocytes and in the control of immune cell homeostasis. Several studies have shown that anticancer therapies require functional cell death signalling pathways. Irradiation based therapy has been successful in treatment of several malignancies but the usage of high doses has been associated with side effects. Therefore, low dose therapies, that either is optimized for specific delivery or administrated in combination with other treatments, are promising modalities. However, in order to achieve high-quality effects of such treatments, the death effector mechanisms involved in tumour eradication needs to be further explored. Importantly, tumour cells frequently acquire resistance to apoptosis, which consequently allows tumour cells to escape from elimination by the immune system and/or treatment. Interferons constitute a large family of pleotrophic cytokines that are important for the immune response against viruses and other microorganisms. The interferon signalling pathway mediates transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. Interferon has successfully been used in therapy against some tumours. However, several drawbacks have been reported, such as reduced sensitivity to interferon during treatment. The aim of this thesis was to elucidate mechanisms that mediate resistance to death receptor or interferon induced apoptosis in human tumour cell models, as well as investigate what molecular events that underlie cell death following radiation therapy of tumour cells. In order to elucidate mechanisms involved in acquired resistance to Fas- or interferon-induced apoptosis, a Fas- and interferon-sensitive human cell line, U937, was subjected to conditions where resistance to either Fas- or interferon induced apoptosis was acquired. Characterization of the Fas resistant cells showed that multiple resistant mechanisms had been acquired. Reduced Fas expression and increased cFLIP expression, which is an inhibitor of death receptor signalling, were two important changes found. To further examine the importance of these two alterations, clones from the Fas resistant population were established. The reduced Fas expression was determined to account for the resistant phenotype in approximately 70% of the clones. In the Fas resistant clones with normal Fas expression, the importance of an increased amount of the cFLIP protein was confirmed with shRNA interference. A cross-resistance to death receptor induced apoptosis was detected in the interferon resistant variant, which illustrates that a connection between death receptor and interferon induced apoptosis exists. Notably, interferon resistant cells also contained increased cFLIP expression, which were determined to mediate resistance to both interferon and death receptor mediated apoptosis. Finally, when cell death induced by irradiation treatment was investigated in HeLa Hep2 cells we could demonstrate that cell death was mediated by centrosome hyperamplification and mitotic aberrations, which forced the cells into mitotic catastrophes and delayed apoptosis. In conclusion, we have described model systems where selection for resistance to Fas or interferon induced apoptosis generated a heterogeneous population, where several signalling molecules were altered. Furthermore, we have shown that a complex cell death network was activated by irradiation based therapy.
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| 48. |
- Carlsen Misic, Martina, 1986-, et al.
(författare)
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Clonidine as analgesia during retinopathy of prematurity screening in preterm infants (cloROP) : protocol for a randomised controlled trial
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Preterm infants are at risk of negative consequences from stress and pain at the same time as they often are in need of intensive care that includes painful interventions. One of the frequent painful procedures preterm infants undergo is eye examination screening to detect early signs of ROP (retinopathy of prematurity). These examinations are both stressful and painful, and despite a multitude of research studies, no conclusive pain-relieving treatment has been demonstrated. The main aim of this trial is to investigate the analgesic effect of clonidine during ROP eye examinations.Methods and analysis The planned study is a multicentre randomised controlled trial with a crossover design. Infants will be recruited from two different neonatal intensive care units (NICUs) in Sweden. Infants born before gestation week 30 (and therefore eligible for ROP screening) and cared for in either of the NICUs will be eligible for inclusion in the study. The primary outcome will be Premature Infant Pain Profile–Revised score within 30 s after starting the examination. Secondary outcomes will be changes in the galvanic skin response parameters (area small peaks, area huge peaks, peaks per second and average rise time) within 30 s after starting the eye examination, together with the number and evaluation of adverse events reported within 72 hours after the examination and the examining physician’s assessment of how easy the infant was to examine.Ethics and dissemination Approval from the Swedish Ethical Review Authority and the Swedish Medical Products Agency has been obtained for the study. Parents of eligible infants will be getting both verbal and written information about the study including that participation is voluntary. Data will be collected and treated in accordance with the European general data protection regulations. The results will be reported on group level and published in a scientific journal.
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| 49. |
- Carlsen Misic, Martina, 1986-, et al.
(författare)
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Clonidine as analgesia during retinopathy of prematurity screening in preterm infants -cloROP
- 2024
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Konferensbidrag (refereegranskat)abstract
- BackgroundPreterm infants are vulnerable and sensitive to stimuli, during their stay in neonatal intensive care they undergo frequent stressful and painful procedures. One of these painful procedures is the screening for retinopathy of prematurity, ROP. In Sweden all preterm infants born before gestation week 30 undergo ROP-screening. The screening involves regular eye examinations to detect ROP at the early stages and these examinations are both stressful and painful. Several studies have investigated different ways of pain management during eye examinations with inconsequent results. No study has investigated Clonidine as pain management during ROP-screening. AimThe aim of this clinical trial is to investigate the analgesic effect of clonidine during ROP eyeexaminations.MethodThis study is a multicenter randomized controlled clinical trial with a crossover design. Infants born before gestation week 30 and therefore undergoing ROP-screening, will be eligible for inclusion in the study. Infants will be recruited from two Swedish NICUs (neonatal intensive care units). The NICUs use different examination techniques, where NICU A uses indirect ophthalmoscopy while NICU B uses RetCam. A total of 50 infants will be recruited (25 at each NICU). During the first eye examination the infant will be randomized to either clonidine 4mcg/kg or sterile water in the equivalent dose 60 minutes before the eye examination. The order of the treatment is blinded for everyone except the nurse preparing the study solution. During the second eye examination the infant will receive the study solution, (intervention or placebo) that he/she did not receive the first time. The primary outcome of the study is pain assessment with the Premature Infant Pain Profile – Revised. The infants´ face and monitor showing oxygen saturation and heart rate will be videorecorded to be able to assess the pain afterwards. The secondary outcome is Galvanic Skin Response where three probes are attached to the infant’s foot sole to register changes in the sweat gland activity in response to stimuli such as pain or stress. The ophthalmologist performing the eye examination will also rate how easy it was to examine the infant by marking an X on a 10cm VAS scale with “very easy to examine” on one end and “very difficult to examine” on the other end. Data collection is ongoing with 19 infants included at the moment.
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| 50. |
- Degerstedt, Oliver, et al.
(författare)
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Quantitative imaging of doxorubicin diffusion and cellular uptake in biomimetic gels with human liver tumor cells
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Novel tumor-on-a-chip approaches are increasingly used to investigate tumor progression and potential treatment options. To improve the effect of any cancer treatment it is important to have an in-depth understanding of drug diffusion, penetration across the tumor extracellular matrix and cellular uptake. In this study, we have developed a miniaturized chip where drug diffusion and cellular uptake in different hydrogel environments can be quantified at high resolution using live imaging. Diffusion of doxorubicin was reduced in a biomimetic hydrogel mimicking tissue properties of cirrhotic liver and early stage hepatocellular carcinoma (362 ± 109 µm2/s) as compared to an agarose gel (571 ± 145 µm2/s, p = 0.0085). The diffusion was further lowered to 164 ± 33 µm2/s (p = 0.0023) by preparing the biomimetic gel in cell media instead of phosphate buffered saline. The addition of liver tumor cells (Huh7 or HepG2) to the gel, at two different densities, did not significantly influence drug diffusion. Clinically relevant and quantifiable doxorubicin concentration gradients (1-20 µM) were established in the chip within one hour. Intracellular increases in doxorubicin fluorescence correlated with decreasing fluorescence of the DNA-binding stain Hoechst 33342, and based on the quantified intracellular uptake of doxorubicin an apparent cell permeability (9.00 ± 0.74 x 10-4 µm/s for HepG2) was determined.
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